title: Nuclear and nucleoid localization are independently conserved functions in bacteriophage terminal proteins.
abstract: Bacteriophage terminal proteins (TPs) prime DNA replication and become covalently linked to the DNA 5'-ends. In addition, they are DNA-binding proteins that direct early organization of phage DNA replication at the bacterial nucleoid and, unexpectedly, contain nuclear localization signals (NLSs), which localize them to the nucleus when expressed in mammalian cells. In spite of the lack of sequence homology among the phage TPs, these three properties share some common features, suggesting a possible evolutionary common origin of TPs. We show here that NLSs of three different phage TPs, Φ29, PRD1 and Cp-1, are mapped within the protein region required for nucleoid targeting in bacteria, in agreement with a previously proposed common origin of DNA-binding domains and NLSs. Furthermore, previously reported point mutants of Φ29 TP with no nuclear localization still can target the bacterial nucleoid, and Cp-1 TP contains two independent NLSs, only one of them required for nucleoid localization. Altogether, our results show that nucleoid and nucleus localization sequence requirements partially overlap, but they can be uncoupled, suggesting that conservation of both features could have a common origin but, at the same time, they have been independently conserved during evolution.
authors.affiliation: Centro de Biología Molecular 'Severo Ochoa' (Consejo Superior de Investigaciones Científicas - Universidad Autónoma de Madrid), Universidad Autónoma, Cantoblanco, 28049, Madrid, Spain.
authors.forename: Modesto
authors.initials: M
authors.lastname: Redrejo-Rodríguez
authors.forename: Daniel
authors.initials: D
authors.lastname: Muñoz-Espín
authors.forename: Isabel
authors.initials: I
authors.lastname: Holguera
authors.forename: Mario
authors.initials: M
authors.lastname: Mencía
authors.forename: Margarita
authors.initials: M
authors.lastname: Salas
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D017103:Bacillus Phages / Q000378:metabolism; D025622:Bacteriophage PRD1 / Q000235:genetics / Q000378:metabolism; D001435:Bacteriophages / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D019913:Nuclear Localization Signals; D017354:Point Mutation; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D019913:Nuclear Localization Signals; D014764:Viral Proteins